Treatment-Related Adverse Effects in Psychotherapy for Chronic Pain: A Comparative Analysis of Different Interventions

Background: Chronic pain affects ~20% of the global population and is frequently associated with psychological comorbidities. While Cognitive Behavioural Therapy (CBT) is widely used, other psychotherapeutic approaches are increasingly applied, including individual Eye Movement Desensitization and Reprocessing (EMDR), group-based Pain Extinction and Retraining Therapy (PERT), and digital Ecological Momentary Interventions (EMI). Despite growing implementation of psychological treatments in chronic pain, little is known about their potential side effects, which are relevant for clinical safety and patient well-being.Methods: Within the multicentre PerPAIN project, side effects of three 12-week psychotherapeutic interventions (individual EMDR, group-based PERT, digital EMI) were investigated in chronic musculoskeletal pain patients. Participants were stratified by pain-related subgroups (adaptive copers, distressed, dysfunctional) and randomised to personalised or non-personalised treatment. Adverse effects were assessed post-treatment using the Negative Effects Questionnaire (NEQ) and Inventory for the Evaluation of Negative Effects in Psychotherapy (INEP). The Patient Global Impression of Change (PGIC) evaluated subjective perception of change to identify perceived deterioration. Statistical analyses included ANOVA, ANCOVA and Kruskal-Wallis tests, controlling for confounding factors.Results: Of the 91 treated participants, 67% reported at least one side effect, most commonly poor sleep, stress, or anxiety. The overall intensity of reported side effects was low, with a mean NEQ total score of 4.51 (SD = 7.28) on a scale ranging from 0 to 128. There were no statistically significant differences in NEQ or INEP scores between EMDR, PERT, and EMI. Older age was associated with fewer NEQ-reported effects (p = .05), whereas higher levels of education were linked to lower pain severity. According to PGIC ratings, 20% of participants reported overall deterioration and 20% pain worsening, with higher educational level predicting less perceived worsening (p < .01). No severe adverse events related to the interventions were observed.Conclusion: Adverse effects were predominantly mild to moderate across all interventions, with no serious treatment-related events observed. No significant differences were found between individual (EMDR), group-based (PERT), and digital (EMI) formats regarding frequency or intensity of adverse effects. Notably, the minimal digital intervention showed no increased negative effects, suggesting treatment intensity may not determine adverse responses. No systematic differences emerged between personalised versus non-personalised assignments or among pain subgroups. These findings indicate the interventions were generally safe and well-tolerated across formats and patient profiles. Future research should identify predictors of negative effects to optimize treatment allocation for safety and therapeutic benefit.